Keywords: Genotype 4, Hepatic fibrosis, Hepatitis C virus, Interleukin-28B, rs12979860 INTRODUCTION Hepatitis C virus genotype 4 (HCV-G4) is the most common type of HCV in the Middle East and Africa, particularly in Egypt, which has the highest prevalence of HCV worldwide (15%), and HCV-G4 represents 90% of all HCV cases[1]. Despite the development of new direct antiviral selleck screening library agents such as protease inhibitors, which have improved response in HCV genotypes[1,2], unfortunately G4 has emerged as a resistant genotype to new treatment strategies. This raises the importance, both for patient care and the economic approach, of improving the prediction of response to standard pegylated interferon alfa (PEG-IFN) and ribavirin therapy.

Although the mechanisms leading to clearance of acute HCV infection are not completely understood, both innate and adaptive immune responses have been suggested to play crucial roles in viral eradication and response to treatment[3]. Besides immune responses, other host factors have also been associated with treatment-induced viral clearance. Higher rates of viral resolution have been reported in women compared with men; however, other factors such as age, race, or route of transmission were not significantly associated with viral resolution[4]. Recently, another host factor, a genetic variation in the interleukin-28B (IL28B) gene, was found to predict spontaneous clearance of HCV infection[5]. A single nucleotide polymorphism (SNP) rs12979860 located 3 kb upstream of IL28B, the gene that encodes IFN-��3, has been strongly associated with resolution of HCV infection[6].

Patients with C/C genotype were more likely to eradicate HCV than those with T/T genotype[7,8]. The same SNP has also been associated with treatment-induced viral clearance[9,10]. Patients with the C/C genotype were twice as likely to achieve an sustained viral response (SVR) compared to patients with other IL28B SNP genotypes[6]. These findings jointly suggest a role for IFN-�� in the innate control of HCV. Of note, the T/T genotype was shown to be more common among those with African ancestry[5]. However, the association between IL28B genotype Drug_discovery and response to treatment among individuals infected with HCV-G4 still needs further investigation among the ethnic group living in the Middle East. Therefore, we conducted the present study to assess the extent of the association between IL28B genotype and response to treatment in HCV-G4 and severity of liver fibrosis. MATERIALS AND METHODS Subjects The study included 201 Egyptian patients with chronic HCV genotype-4 who were followed in the Hamad Medical Corporation outpatient clinic in the State of Qatar. Patients received HCV treatment between 2007 and 2010.